The major ligand-receptor systems involved in uptake of the intracellular pathogens Trypanosoma cruzi, Salmonella and Toxoplasma gondii by phagocytic and non-phagocytic cells were examined. Earlier experiments with T. cruzi were extended by showing that purified C1q enhances uptake of trypomastigotes but not epimastigotes into human foreskin fibroblasts. The acute phase reactant, mannose binding protein (MBP), binds to mannose rich but not mannose poor isolates of Salmonella. MBP bound to Salmonella functions as a direct opsonin for ingestion by neutrophils, possibly by binding to neutral glycolipids in the neutrophil. MBP, at concentrations found in normal human serum, augments deposition of C3 on the Salmonella by over 3 fold. Despite the overall structural similarity between MBP and classical complement pathway subcomponent C1q, augmentation is mediated entirely by the alternative pathway. MBP sensitization converts organisms ordinarily resistant to serum bactericidal activity to serum susceptible status. The basement membrane protein, laminin, markedly augments attachment and entry of tachyzoites of Toxoplasma gondii into macrophages and fibroblasts. Laminin binds to a 65-60kD surface iodinatable protein on tachyzoites which is not extractable with non-denaturing detergents. This molecule is recognized by an antibody to the ubiquitous 67kD laminin binding protein present on a variety of mammalian cells.